Outcomes of cardiac surgery in patients age ≥80 years: results from the National Cardiovascular Network

AbstractOBJECTIVESThe purpose of this study was to evaluate characteristics and outcomes of patients age ≥80 undergoing cardiac surgery.BACKGROUNDPrior single-institution series have found high mortality rates in octogenarians after cardiac surgery. However, the major preoperative risk factors in this age group have not been identified. In addition, the additive risks in the elderly of valve replacement surgery at the time of bypass are unknown.METHODSWe report in-hospital morbidity and mortality in 67,764 patients (4,743 octogenarians) undergoing cardiac surgery at 22 centers in the National Cardiovascular Network. We examine the predictors of in-hospital mortality in octogenarians compared with those predictors in younger patients.RESULTSOctogenarians undergoing cardiac surgery had fewer comorbid illnesses but higher disease severity and surgical urgency than younger patients. Octogenarians had significantly higher in-hospital mortality after cardiac surgery than younger patients: coronary artery bypass grafting (CABG) only (8.1% vs. 3.0%), CABG/aortic valve (10.1% vs. 7.9%), CABG/mitral valve (19.6% vs. 12.2%). In addition, they had twice the incidence of postoperative stroke and renal failure. The preoperative clinical factors predicting CABG mortality in the very elderly were quite similar to those for younger patients with age, emergency surgery and prior CABG being the powerful predictors of outcome in both age categories. Of note, elderly patients without significant comorbidity had in-hospital mortality rates of 4.2% after CABG, 7% after CABG with aortic valve replacement (CABG/AVR), and 18.2% after CABG with mitral valve replacement (CABG/MVR).CONCLUSIONSRisks for octogenarians undergoing cardiac surgery are less than previously reported, especially for CABG only or CABG/AVR. In selected octogenarians without significant comorbidity, mortality approaches that seen in younger patients

Coronary-artery bypass surgery in patients with ischemic cardiomyopathy

BACKGROUND The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear. METHODS From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy alone (medical-therapy group, 602 patients). The primary outcome was death from any cause. Major secondary outcomes included death from cardiovascular causes and death from any cause or hospitalization for cardiovascular causes. The median duration of follow-up, including the current extended-follow-up study, was 9.8 years. RESULTS A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in 398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P=0.02 by log-rank test). A total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006 by log-rank test). Death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524 patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82; P<0.001 by log-rank test). CONCLUSIONS In a cohort of patients with ischemic cardiomyopathy, the rates of death from any cause, death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes were significantly lower over 10 years among patients who underwent CABG in addition to receiving medical therapy than among those who received medical therapy alone. (Funded by the National Institutes of Health; STICH [and STICHES] ClinicalTrials.gov number, NCT00023595.

The impact of privacy and confidentiality laws on the conduct of clinical trials.

Justifiable concerns about the use of personal data in many aspects of daily life have led to the recent introduction in many countries of laws intended to regulate data use. Although participation in randomized clinical trials is generally with informed consent, recruitment procedures, complete follow-up, and the efficient conduct of trials may be substantially affected by such national or local privacy legislation. The relevant laws often have exceptions that allow the use of patient information in the public interest - including the use of data collected to improve or monitor public health or as part of medical research. However, regulatory bodies often give conflicting interpretations of the law, and this affects the conduct of large-scale trials. In particular, unnecessarily restrictive interpretation of the law may be a serious impediment to identification of potential participants for a trial, access to records to confirm events, continued follow-up of patients after the trial has been concluded, and secondary use of the trial data for purposes not directly related to the original purpose of the study. These obstacles could be overcome by better informing patients of the uses of records for medical research purposes, by using informed consent procedures that explain the nature of the research and the uses of the data, and by the use of identifiers, such as social security numbers that allow central follow-up. The clinical trial research community needs to ensure that the substantial benefits of large-scale randomized trials are explained both to the public and to those responsible for introducing legislation. The negative impact of privacy legislation on the use of personal health information and on conducting large studies needs to be understood and minimized

Effect of clinical factors on length of stay after coronary artery bypass surgery: results of the cooperative cardiovascular project

BACKGROUND: Rising health care costs have prompted careful review of comparative hospital resource use. Length of stay after bypass surgery has received particular attention. However, many providers assert that these variations are caused by differences in the clinical mix of patients treated. Our goals were to identify the major clinical predictors of postoperative length of stay (PLOS) after coronary artery bypass graft surgery (CABG), document variations in PLOS among 28 hospitals, and assess the degree to which patient characteristics account for hospital variations in PLOS. METHODS: Detailed clinical data on 3605 Medicare patients undergoing CABG in 28 Alabama and Iowa hospitals were analyzed by stepwise linear regression to identify significant clinical predictors of PLOS. Analysis of variance was used to compare hospitals\u27 PLOS while controlling for significant patient risk factors. RESULTS: The mean age was 72.1 years, 34.7% were female, and the in-hospital mortality rate was 5.6%. The median and mean PLOS were 8 and 11.1 days, respectively. Significant predictors of longer PLOS included increasing age, female sex, history of chronic obstructive pulmonary disease, cerebrovascular disease, or mitral valve disease, elevated admission blood urea nitrogen, and preoperative placement of an intraaortic balloon pump. Hospitals varied significantly (P =.0001) in their unadjusted PLOS. These hospital-level variations persisted despite adjustment for both preoperative patient characteristics (P =.0001) and postoperative complications and death (P =.0001). CONCLUSIONS: This study found significant between-hospital variations in PLOS that were not explained by patient factors. This finding suggests the potential for increased efficiency in the care of patients undergoing CABG at many institutions. Further research is needed to determine the practice patterns contributing to variations in length of stay after bypass surgery

Activity of VNP40101M (Cloretazine) in the treatment of CNS tumor xenografts in athymic mice

VNP40101M, or 1,2-bis(methylsulfonyl)-1-(2-choloro-ethyl)-2-(methylamino)carbonylhydrazine (Cloretazine), is a bifunctional prodrug that belongs to a class of DNA-modifying agents—the sulfonylhydrazines—that has been synthesized and been shown to have activity against a wide spectrum of xenografts. The current study was designed to assess the activity of VNP40101M administered at a dose of 18 mg/kg daily for five days against a panel of human adult and pediatric CNS tumors growing subcutaneously or intracranially in athymic nude mice. The results demonstrated statistically significant (p < 0.05) growth delays of 15.0, 8.3, 51.0, 60+, 60+, and 60+ days in subcutaneous xenografts derived from childhood glioblastoma multiforme (D-456 MG), childhood ependymoma (D-528 EP and D-612 EP), childhood medulloblastoma (D-425 MED), and adult malignant glioma (D-245 MG and D-54 MG), respectively, with corresponding tumor regressions in 10 of 10, 4 of 10, 8 of 10, 9 of 10, 9 of 10, and 10 of 10 treated mice, respectively. Delayed toxicity was seen more than 60 days after treatment, with 23 deaths in 100 treated animals, despite a median weight loss of only 0.06%. In mice bearing intracranial D-245 MG xenografts, treatment with VNP40101M at a dose of 18 mg/kg daily for five days produced a 50% increase in median survival compared with controls. Additional experiments conducted against subcutaneous D-245 MG xenografts by using reduced doses of 13.5 or 9.0 mg/kg daily for five days demonstrated tumor growth delays of 82.2 and 53.5 days, with corresponding tumor regressions in 8 of 9 and 9 of 10 treated mice, respectively (all values, p < 0.001), with one toxic death. These findings suggest that VNP40101M is active in the treatment of a wide range of human central nervous system tumors and warrants translation to the clinic

Re-evaluating the volume-outcome relationship in hemodialysis patients

Objectives We sought to determine whether dialysis patient mortality rates are associated with differences in dialysis facility size, and whether this relationship differs among higher risk diabetic and lower-risk non-diabetic patients.Methods Using 186,554 adult end-stage renal disease patients initiating hemodialysis at standalone facilities in the United States between 1996 and 1999, we evaluated relationships between dialysis facility size and survival to 5 years. We performed separate analyses for patients with and without diabetes as their primary cause of end-stage renal disease. Facility size was defined according to the number of hemodialysis patients at year's end (small =120).Results Increasing facility size was associated with a reduced risk of mortality at 4 years for both diabetic (HR = 0.983 per 10 unit increase, 95% CI = 0.967, 0.999) and non-diabetic patients (HR 0.977 per 10 unit increase, 95% CI = 0.963, 0.992) dialyzing in small facilities, and for diabetic patients (HR 0.989 per 10 unit increase, 95% CI = 0.980, 0.998) dialyzing in medium size facilities.Conclusions Smaller facility size is associated with increasing long-term mortality for in-center hemodialysis patients. This relationship appears to be more pronounced among higher-risk diabetic vs. lower-risk non-diabetic patients.Hemodialysis End-stage renal disease Health facility size Practice management